The long-term objectives of this research program are to define the extent to which the dental pulp regulates the development, maintenance, and repair of its innervation and to elucidate the mechanisms for this regulation. The underlying hypothesis is that nerve growth factor (NGF) or other neuronotrophic factors act as mediators by which dental tissues influence the neurons which innervate them. In recent years, the dependence of peripheral sympathetic and sensory neurons on such factors from other target tissues has been demonstrated. The specific aims of the proposed studies are (1) to determine whether those sympathetic and sensory neurons which innervate the dental pulp are dependent on NGF during the developmental period when the innervation to the pulp is established and (2) to determine whether reinnervation of the pulp following nerve injury is dependent on availability of NGF. The question of NGF dependence of neurons innervating the pulp will be addressed by assessing the consequences of NGF deprivation on the development and recovery from injury of intradental innervation of the rat molar. A condition of NGF deprivation will be accomplished using the well-established autoimmune model. Rats deprived of endogenous NGF in utero and neonatally will be anatomically evaluated for deficits in (1) neuron populations in the trigeminal and superior cervical ganglia and (2) in myelinated and unmyelinated nerve fiber numbers in the first mandibular molar, inferior alveolar nerve, and mental nerve. The proposed studies will further distinguish between immediate and permanent effects of NGF deprivation and effects of prenatal versus postnatal NGF deprivation. The possibility that NGF dependence is restricted to specific sub-populations of neurons innervating the pulp will also be explored. The possibility of an essential role of NGF in repair of dental nerve injury will be tested by evaluating recovery from inferior alveolar nerve section in mature animals deprived of endogenous NGF. These studies will advance understanding of the complex interactions between dental tissues and the neurons that innervate them.